The endothelium modulates vascular homeostasis through the release of different factors, including vasoactive prostanoids. These substances may regulate vascular tone and other vascular processes. The aims of this study were to assess the contribution of vasoactive prostanoids to vascular tone in normal humans and to determine whether this regulatory activity is dysfunctional in conditions associated with premature atherosclerosis, such as essential hypertension and hypercholesterolemia. To this end, we investigated the effect of cyclooxygenase inhibition with increasing doses of aspirin (ASA; infused at 1, 3, and 10 mg/min, each dose for 10 min) on resting vascular tone in 10 healthy subjects (age: 49+/-7 years, 6 men and 4 women), 9 hypertensive (age: 51+/-5 years, 5 men and 4 women), and 10 hypercholesterolemic patients (age: 54+/-4 years, 7 men and 3 women). ASA was infused into the brachial artery, and forearm blood flow (FBF) was measured by strain gauge plethysmography (values=mean+/-sd). At the highest dose, ASA decreased resting FBF in healthy subjects from 2.8+/- 0.9 to 2.3+/-0.7 ml/min/dl (p=0.04); in hypertensive patients from 2.9+/-0.9 to 2.3+/-0.8 ml/min/dl (p=0.05); and in hypercholesterolemic patients from 3.0+/-0.6 to 2.2+/-0.6 ml/min/dl (p<0.0001). The hemodynamic effect of ASA was not different between healthy subjects, and hypertensive or hypercholesterolemic patients (reduction in FBF: 14+/-28%, 14?28%, and 27+/-14%, respectively; p=0.40). These findings suggest that vasodilator prostanoids derived from cyclooxygenase metabolism play a role in the maintenance of resting microvascular tone in humans. This physiologic process does not seem to be altered in patients with essential hypertension or in those with hypercholesterolemia. - prostanoids hypertension hypercholesterolemia blood vessels - Human Subjects